Contraceptive methods involving the administration of chemical substances are widely practiced among women who desire to limit pregnancies. Such methods control fertility through various biological mechanisms. Among the presently used chemical methods of fertility control, the most important are those which act by means of the following: (a) suppression of ovulation through inhibition of gonadotropin release; (b) alteration of the female reproductive tract to prevent migration of sperm to the site of fertilization or, if fertilization occurs, to block implantation of the zygote (nidation); or (c) spermicidal action.
The oral contraceptives are the most prominent chemical contraceptive agents. These agents are of two types both involving the use of female sex hormones: (a) an estrogen combined with a progestin, and (b) a progestin alone. The contraceptives of the combined type act primarily by suppressing ovulation via negative feedback to prevent gonadotropin (LH and FSH) release by the hypothalamus, but alterations in the reproductive tract may also contribute to the antifertility effect. Such alterations include changes in the cervical mucus (which increase the difficulty of sperm migration) and in the endometrium (which decrease the likelihood of nidation). The action of a progestin alone in a very low oral dose (the "mini-pill") appears to involve primarily alterations in the female reproductive tract, but ovulation suppression may also occur. Although the oral contraceptives are highly effective, their use is associated with unpleasant side effects, including nausea, depression, weight-gain, and headache, plus an increased long-term risk of severe disease such as thromboembolism, stroke, myocardial infarction, hepatic adenoma, gall bladder disease, and hypertension. Bleeding irregularities, e.g., breakthrough bleeding, spotting, and amenorrhea, are also frequent. A progestin, when administered alone, may also cause an increased incidence of changes in menstrual patterns, especially a marked increase in the amount and duration of menstrual bleeding.
Besides the oral route of administration, a progestin alone may be administered systemically by various sustained-release dosage forms which include among other forms: (a) depot injection (IM) of an insoluble progestin (e.g., medroxy progesterone acetate), or (b) subdermal implant. With these methods of administration, the progestin is absorbed into the body continuously at a very low daily dose, and the systemic effects are similar to those produced by oral administration of a progestin. However, as with the oral progestins, since a hormone is still the active agent, these sustained release methods may also cause serious menstrual flow irregularities.
Other chemical methods of contraception include the postcoital administration of estrogens; e.g., diethylstilbestrol or ethynylestradiol. These estrogens act to prevent nidation. Prostaglandins which act as abortifacients are also administered postcoitally. Both of these methods, at present, are limited to emergency situations. Still in the very early stages of development are immunological methods of contraception (vaccination) and methods involving the direct control of LHRH secretion from the pituitary by LHRH agonists or antagonists.
Another group of chemical contraceptive agents in common use are the local spermicides, such as nonoxynol or octoxynol, which are placed in the vagina immediately prior to coitus in the form of creams, foams, jellies, or suppositories containing the spermicide. The spermicidal action takes place either in the vagina or elsewhere in the reproductive tract. For the latter to occur, the spermicidal agent is either adsorbed on sperm membranes or is transported into the uterus under the influence of uterine contractions. The spermicidal methods are not altogether reliable in preventing pregnancy and are inconvenient to use.
The most common alternative to the use of oral contraceptives is the intrauterine device (IUD). Except when composed of copper, the anti-fertility effect of the IUD is not caused by chemical activity. Instead, the material forming the IUD induces a foreign body reaction (irritation) in the contiguous endomentrium which appears to interfere in some way with nidation. The use of the IUD is complicated, however, by serious side effects including the possibility of uterine perforation, pelvic inflammation, discomfort, and aggravated menstrual periods.
Many of the above chemical contraceptive agents can be administered via intrauterine or intravaginal devices which pay out the contraceptive at a steady rate for at least 21 days, the average time between menstrual periods in the human female. A recently introduced method of contraception involves the sustained release of progesterone locally within the uterine lumen. In this method, the progesterone is incorporated into a chamber within a flexible intrauterine device (IUD) formed from a polymer which is capable of releasing progesterone continuously into the uterine fluids at a slow rate over a prolonged period of time. The progesterone acts primarily locally to produce progestational alterations in the cervical mucus and endometrium. However, the antifertility action may also be caused by the reaction of the endometrium to the device itself ("IUD effect") or by systemic absorption of progesterone through the uterine membrane. Again, as with other progestin-only therapies, there is an increased incidence of menstrual flow irregularities. Another disadvantage of this contraceptive method, is the increased risk of ectopic pregnancy.
Recently a new device, the flexible IUD bearing metallic copper, has come into widespread use. The contraceptive action of this device results from the combined effects of the copper, which very slowly in the uterine fluids, acting on the blastocyst as well as the cervical mucus or endometrium, and of the IUD itself, which causes a foreign body reaction in the endomentrium.